(1)The cortical auditory system is far more extensive than expected, as it includes not only the entire superior temporal gyrus but also large portions of the parietal, prefrontal, and limbic lobes. Several of these areas overlap with previously identified visual areas, suggesting that the auditory system, like the visual, contains separate pathways for processing stimulus quality and stimulus location. (2) This division between stimulus quality and stimulus location processing was demonstrated for auditory working memory. Human subjects were asked to remember the identity of voices or of their location in an fMRI study. (3) Monkeys, like humans, appear to use the auditory system of the left hemisphere preferentially to process vocalizations. This functional asymmetry was demonstrated in monkeys by comparing metabolic rates, using FDG and PET scanning in the two hemispheres while the animals listened to conspecific calls compared with numerous other sound classes. Within the superior temporal gyrus, greater metabolic activity occurred on the left side than on the right only in the region of the temporal pole and only in response to monkey calls. New experiments using high-field fMRI demonstrates that we can map the reversal in frequency representation (i.e. high-low-high) known to occur at the junction of A1 and R in the core area of the monkey auditory cortex. These results are consistent with results in humans using fMRI suggesting that parallel neuroimaging experiments is likely to facilitate the application to humans of the accumulating auditory neurobiological information being acquired in monkeys. (4) Monkeys trained on a task designed to assess auditory recognition memory, were impaired after removal of either the rostral superior temporal gyrus (rSTG) or the medial temporal lobe (MTL) but were unaffected by lesions of the rhinal cortex (Rh). These results compared with those obtained in other sensory modalities, in which Rh lesions produce severe impairment, lead to the tentative conclusion that the monkeys in this auditory study were unimpaired after Rh lesions because they had performed the task utilizing short-term or working memory rather than long-term recognition memory. Monkeys learn the rule for visual and tactile versions of trial-unique delayed matching- and nonmatching-to-sample at short delays within a few hundred trials and then show forgetting thresholds (i.e. scores falling to 75% accuracy) at delays of 10 min or more. By contrast, on our auditory version of delayed matching-to-sample monkeys required 15,000 trials to learn the rule and then had forgetting thresholds of only about 35s. We trained monkeys on auditory DMS using various training methods. Independent of the procedure the average number of trials needed to perform at greater than 80% accuracy at 5s was 20,000 and forgetting thresholds still averaged about 30s. These results suggest that the procedures alone are unlikely to account for the difficulty to learn auditory DMS. Further comparisons indicate that a normal monkey performing our version of auditory DMS resembles a monkey with Rh cortical lesions performing visual DMS; neither seems able to store long-term stimulus representations. This inability suggests that the auditory stimuli were processed without the participation of the Rh cortices and consequently ablating the Rh cortices had no deleterious effect. The correlate of this proposal is that, like the residual mnemonic ability in vision after Rh lesions, the mnemonic ability in audition observed here in normal monkeys rests entirely on mechanisms mediating short-term or working memory. This proposal that performance on our auditory DMS task was based on working memory implies it is the form of memory that impaired after both the rSTG and MT lesions. This implication after rSTG lesions is consistent with the anatomical position occupied by rSTG in the cortical auditory system. That is, from a series of anatomical studies it appears that rSTG may be a late station in the ventral processing stream for audition much like area TE is for vision, and so it is highly likely that rSTG serves an important role in short-term auditory memory just as area TE does in short-term visual memory. The impairment produced by the MT ablation may have been a result from collateral damage and not hippocampal damage, such as severing the projections of rSTG to downstream areas in the prefrontal cortex, medial thalamus, or both. An anatomical study has confirmed that an MT removal does indeed disconnect rSTG anatomically from several prefrontal and medial thalamic areas. (5) An important aspect of auditory processing is the spectral and temporal integration of acoustic information. We recorded neuronal responses to (a) pure tones and bandpassed noise in order to obtain frequency tuning curves (FTCs), (b) ripple stimuli in order to generate spectrotemporal receptive fields (STRFs), and (c) linear frequency modulated (FM) stimuli, which are natural components of monkey calls. Cortical neurons showed a variety of temporally structured types of response, including tonic, pauser, and offset responses, which appear to have different distributions in the two primary auditory areas, A1 and R. Although most of the neurons respond preferentially to a single best frequency, some neurons (10-15%) show multiple tuning peaks both in their FTCs and STRFs, suggesting that these neurons integrate spectral information over a wide range of frequencies, which may be important in mediating auditory pattern recognition. Also, 75% of A1 and R neurons were selective for FM direction and/or rate, with response distributions suggesting that rate and directionality are independently represented in monkey primary auditory cortex. (6) Neuronal representation of auditory stimulus-quality was assessed in the rSTG. Monkeys performed an auditory discrimination task using a single positive stimulus (white noise) and 44 negative stimuli including monkey calls (MC) and other complex stimuli (OA). 53% of the neurons recorded showed significant responses to auditory stimuli, 16% responded only to MC, 17% to OA stimuli and 12 % to both MC and OA. Units that responded only to MC or OA responded to only 1 or 2 sounds and more than half of were inhibitory responses. Neurons that responded to both MC and OA responded to multiple sounds with both excitatory and inhibitory responses. These results indicate that rSTG contains a large portion of highly selective auditory neurons and may represent a late station in the auditory processing stream with neurons that play an important role in the identification of acoustic stimuli. Unlike objects in static visual scenes, auditory objects unfold over time. At the level of the A1 and R, the firing rate of a neuron may track periodic features (e.g. frequency or amplitude modulation), but such tracking is not apparent in neurons rostral to the core auditory fields. We recorded spike trains of single neurons in rSTG to determine if discharge patterns carry stimulus specific information. Monkeys performing a short?term memory task were presented with a stimulus set of 21 sounds. For each of the 21 stimuli, response coefficients were averaged across repeated presentations to determine if temporal characteristics of the response were consistent within stimuli. Compare to randomly drawn bootstrap samples the first PC of nearly all tested units showed a significant effect of stimulus identity. A simple classifier based on waveform shapes suggests that mutual information between response waveform and stimulus identity increases as up to 20 PCs are used. These results suggest that in higher-order sensory cortices, temporal aspects of spike trains may be more important for representing dynamic auditory stimuli than they are for representing static visual images. [unreadable] Publications generated by this research: Fritz J, Mishkin M, Saunders RC (2005) In search of an auditory engram. Proc Natl Acad Sci U [unreadable]